Dataset Information

Adjunctive ibuprofen in pre-extensively drug-resistant and extensively drug-resistant tuberculosis: a Phase IIA open-label pilot clinical trial

ABSTRACT:

Drug-resistant tuberculosis (TB) remains a major global health challenge. Host-directed therapies (HDTs) aim to limit tissue damage, shorten treatment, and improve outcomes by modulating immune responses. We evaluated the safety and potential efficacy of adjunctive ibuprofen an inexpensive, well-tolerated non-steroidal anti-inflammatory drug in pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR)TB. In this prospective, open-label, randomized pilot study (NCT02781909) in Georgia, 28 adults with bacteriologically confirmed pulmonary pre-XDR or XDR-TB were randomized 1:1 to receive standard-of-care (SoC) alone (n=14) or SoC plus ibuprofen 400 mg daily for 2 months (n=14), with 6 months of follow-up. Primary endpoints were sputum culture conversion and radiological improvement. Secondary endpoints included WHO-defined outcomes, safety, health-related quality of life, and inflammatory markers. By month 2, culture negativity was achieved in 27% of controls and 9% of ibuprofen recipients, with median conversion time of 4 months in both groups. Radiological improvement was observed in 64% vs 54% at month 2, and in 90% of both groups by month 6. Final outcomes were comparable (71% cured), and adverse events did not differ. Ibuprofen was associated with reductions in inflammatory markers, including monocyte-to-lymphocyte ratio and interferon gamma. Adjunctive ibuprofen did not improve primary endpoints but showed immune-modulating activity with a favourable safety profile, supporting further investigation in larger studies.

INSTRUMENT(S): Liquid Chromatography MS - positive - HILIC

PROVIDER: MTBLS13376 | MetaboLights | 2026-05-28

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS13376_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13376_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	s_MTBLS13376.txt	Txt

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Project description:Drug-resistant tuberculosis (TB) remains a formidable global health challenge. Host-directed therapies (HDTs) offer the potential to mitigate tissue damage, reduce treatment duration, and improve clinical outcomes by modulating immune responses. We assessed the safety and potential efficacy of adjunctive ibuprofen—an inexpensive, well‐tolerated non-steroidal anti-inflammatory drug—in patients with pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR) TB. In this prospective, open-label, randomized pilot study (NCT02781909) conducted in Georgia, 28 adults with bacteriologically confirmed pulmonary pre-XDR or XDR-TB were randomized 1:1 to receive either standard-of-care (SoC) TB treatment alone (n=14) or SoC plus 400 mg ibuprofen daily during the first 2 months (n=14). Participants were followed for 6 months. The primary endpoints were early sputum culture conversion and radiological improvement. Secondary endpoints included WHO-defined final treatment outcomes, safety, health-related quality of life (HQoL), and changes in inflammatory markers. By week 2, culture negativity was achieved in 27% of control participants versus 9% in the ibuprofen group (risk difference 18%, 95% CI −13 to 50). The median time to culture conversion was 4 months in both groups. At month 2, favourable X-ray evolution was observed in 64% of controls compared with 54% of the ibuprofen group (risk difference 9%, 95% CI −32 to 50), with 90% of participants in each group showing improvement by month 6. Final treatment outcomes were comparable (≈71% cured) and the incidence of safety-related events did not differ significantly. Notably, the ibuprofen group exhibited greater proportional reductions in inflammatory markers—including a statistically significant decrease in the monocyte-to-lymphocyte ratio at months 2 and 5, along with reductions in interferon gamma levels and the enrichment score for Thompson_FAIL_13 gene signature at month 6. Although adjunctive ibuprofen did not improve primary microbiological or radiological endpoints, its excellent safety profile and significant anti-inflammatory effects support its potential role as an immune-modulating adjunct in the treatment of drug-resistant TB. These findings warrant further investigation in larger studies to optimize dosing and evaluate clinical benefits.

Project description:The aim of the longitudinal analysis was to examine the transcriptional blood profile of active TB patients at the time of recruitment (before drug treatment) and then subsequently at specific time points after drug treatment to determine whether the signature is extinguished with treatment and when. Whole blood collected in tempus tubes from patients with different spectra of TB disease and healthy controls. All patients were sampled prior to the initiation of any antimycobacterial therapy. Active Pulmonary TB: PTB - All patients confirmed by isolation of Mycobacterium Tuberculosis on culture of sputum or bronchoalvelolar lavage fluid. Healthy controls - these were volunteers without exposure to TB who were negative by both tuberculin skin test (<15mm if BCG vaccinated, <6mm if unvaccinated); who were also negative by Interferon-Gamma Release assay(IGRA); specifically Quantiferon Gold In-Tube Assay (Cellestis, Australia). Here the aim of the experiment is to assess the longitudinal effect of antimycobacterial treatment on the active TB signature, during and after treatment. Blood was taken from the active TB patients at baseline, pre-treatment, 2 months after treatment inititation, and 12 months after treatment initiation, which would be after treatment was completed. These samples were then amplified at the same time with samples from healthy controls and hybridised to the same chips to permit an assessment of whether the post treatment samples had similar transcriptional profiles to healthy controls or were distinct. In this dataset: PTB baseline, n = 7; PTB 2 months, n = 7; PTB 12 months, n = 7. BCG+ control baseline, n =12. Experimental variables: Patient group: Active PTB; Healthy controls (all BCG vaccinated). ethnicity - a wide range of ethnic groups is represented. The active PTB group incorporates a range of smear positive and smear negative disease and a spectrum of disease extent/severity. Timepoint: 0 months = baseline pre-treatment;2 months = 2 months after initiation of treatment; 12 months = 12 months after initiation of treatment.

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Adjunctive ibuprofen in pre-extensively drug-resistant and extensively drug-resistant tuberculosis: a Phase IIA open-label pilot clinical trial

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